Incidence Of AIDS-related Lymphoma Research Articles

Unique Clinical Implications of HIV-Related Lymphoma

Since the introduction of combination antiretroviral therapy (cART) almost two decades ago, a number of changes have taken place in the spectrum of cancer affecting HIV-infected individuals. Although the incidence and proportion of deaths related to non-AIDS-defining malignancies, mostly infection-related cancers, are increasing, lymphoma is still a major complication of HIV-infection and is the most frequent neoplastic cause of death among HIV-infected individuals [1,2]. A decline in the incidence of lymphoma has been observed in the cART era, along with a concomitant increase in CD4 counts and a decrease of HIV RNA at lymphoma diagnosis. In general, the incidence of non-Hodgkin lymphoma (NHL) initially declined but has eventually stabilized. Nevertheless, the changes in the incidence of AIDS-related lymphoma (ARL) have been heterogeneous among the different lymphoma types. Cases of diffuse large B-cell lymphoma (DLBCL), especially primary CNS lymphoma, have decreased, while the proportion of Burkitt’s lymphoma (BL) cases have increased [3–5]. The incidence of Hodgkin’s lymphoma (HL) has remained stable and even increased in some cohorts [6,7]. This heterogeneity could be explained by the fact that the use of cART has decreased the proportion of HIV-infected individuals with low CD4 counts and, as a consequence, lymphomas that typically presented in severe immunosuppressed patients have diminished as well. This is the case of primary effusion lymphomas, plasmablastic lymphomas and primary CNS lymphoma, all having a higher incidence among patients with severe immunosuppression and poor HIV control. On the other hand, cART would act by increasing CD4 counts thereby facilitating the development of lymphomas with favorable biology and more likely to be cured, such as BL and HL [8]. Some changes have been observed in the presentation of HIV-associated lymphoma in the cART era. Regarding the transmission risk factor, there seems to have been an increase in the proportion of men who have sex with men and a decrease of intravenous drug users [5], probably due to the changes in the spectrum of HIV infection transmission in the population. Patients are older at lymphoma diagnosis, with higher

AIDS-Related Non-Hodgkin's Lymphoma in the Era of Highly Active Antiretroviral Therapy.

In economically developed countries, AIDS-related lymphoma (ARL) accounts for a large proportion of malignances in HIV-infected individuals. Since the introduction of highly active anti-retroviral therapy (HAART) in 1996, epidemiology and prognosis of ARL have changed. While there is a slight increase in the incidence of Hodgkin's lymphoma in HIV-infected individuals, use of HAART has contributed to a decline in the incidence of non-Hodgkin's lymphoma (NHL) and also a decrease in the overall incidence of ARL. Strategies that employ HAART, improved supportive care, and the use of Rituximab with multi-agent chemotherapy have contributed to improved rates of complete remission and survival of patients with ARL that rival those seen in stage and histology matched HIV negative NHL patients. Most recent clinical trials demonstrate better outcomes with the use of rituximab in ARL. Tumor histogenesis (germinal center vs. non-germinal center origin) is associated with lymphoma-specific outcomes in the setting of AIDS-related diffuse-large B cell lymphoma. High-dose chemotherapy (HDCT) and autologous stem cell rescue (ASCT) can be effective for a subset of patients with relapsed ARL. HIV sero-status alone should not preclude consideration of ASCT in the setting of ARL relapse. Clinical trials investigating the role of allogeneic hematopoietic stem cell transplant in ARL are currently underway.

Eleven years of experience with AIDS-related lymphomas at the Institute of Oncology Ljubljana

Neoplastic diseases are currently recognized in more than 40% of HIV sero-positive patients, with AIDS-related lymphomas (ARL) being most common. A survey of the ARLs in patients attending our institute from 1998 to 2009 is given along with the clinical and pathological manifestations, treatment and outcomes. We conducted a retrospective chart review of patients treated for ARL between 1998 and 2009 at the Institute of Oncology Ljubljana. Patients were identified from the lymphoma database of our institute. Eight patients with ARL were diagnosed and treated at our Institute according to the then protocol for HIV sero-negative lymphoma patients. Seven patients received HAART. Six patients received prophylaxis for opportunistic infections and febrile neutropenia (FN), and 6 of them had at least one episode of FN. Seven patients are still alive and in complete remission 7-142 months after the diagnosis of ARL. One of the patients died of progressive lymphoma. The low incidence of ARL in the HIV-infected population, early stages at the presentation and the good response to treatment are not in accordance with the data from the literature. Whether this goes on account of the HAART treatment, prophylaxis for opportunistic infections and FN or a better follow-up of these patients remains to be answered. Also, the group is very small to make any definitive conclusions.

Attenuation of the epidemic increase in non-Hodgkin's lymphomas in Spain

Background: Attenuation of the epidemic increase in non-Hodgkin's lymphoma (NHL) incidence has recently been reported in the USA and Nordic European countries. After two decades of steadily increasing NHL, this study sought to ascertain whether a similar stabilisation might have taken place in Spain in recent years.Patients and methods: NHL cases were drawn from 13 population-based Spanish cancer registries with a record of at least 10 years of uninterrupted registration during the period 1975–2004. Overall and age-specific changes in incidence rates were evaluated using change-point Poisson models, which allow for accurate detection and estimation of trend changes.Results: A total of 21 335 NHL cases (11 531 male and 9804 female) were identified. Although overall age- and registry-adjusted incidence rates rose by 5.74% annually among men and 6.58% among women across the period 1975–95, a statistically significant change-point was nevertheless detected in both sexes in 1996, followed by stabilisation.Conclusions: In Spain, NHL incidence levelled off in 1996 after a sharp increase during the 1970s and 1980s. This stabilisation is, partially at least, linked to the decrease in incidence of AIDS-related lymphomas among young adults.

Abstract 5353: Identification of a subset of AIDS related lymphoma (ARL) containing HIV infected macrophages that is immunophenotypically distinct from EBV+ ARL

Abstract The risk of developing non-Hodgkin lymphoma is 60X greater in the HIV-infected population when compared to non-infected individuals despite the initiation of highly active antiretroviral therapy (HAART). The primary difference between lymphoma in non-infected individuals and those with AIDS related lymphoma (ARL) is that ARL is high-grade and metastatic. Since the introduction of HAART the incidence of ARL has decreased but not the same extent as other AIDS-related malignancies and there has been little change amongst the CD4 strata. Therefore, with the increase in life expectancy afforded by HAART, the overall number of ARL cases is expected to rise in the future. Preliminary reports have suggested that some ARLs contain HIV-infected macrophages that may contribute to ARL pathogenesis. A recent study evaluating HIV sequence evolution in the contest of metastatic ARL found lymphoma specific HIV compartmentalized within sites of lymphoma that was distinct from HIV present in non-lymphoma sites (Salemi et al, PLOSone Dec 3, 2009). These data suggested the existence of a lymphoma specific form of HIV evolving within individuals who develop ARL. The goal of this research was to determine the incidence of HIV infected lymphomas in the pre and post-HAART eras and if HIV-positive lymphomas have a specific immunophenotype. A tissue microarray containing ∼150 of ARLs (from 1982-2007) was obtained through the AIDS and Cancer Specimen Resource (ACSR) and was used for HIV p24 and macrophage CD68 immunohistochemistry. Double staining techniques confirmed that p24 expression was localized to tumor associated macrophages (TAM). There was a highly significant (p<0.001) increase in the frequency of p24+ ARL cases post-HAART (after 1996; 49%) as compared to pre-HAART (before 1996; 26%). Using antigen expression data CD20, CD3, CD10, BCL6, BCL2, MUM1, Ki67, blimp, p53 and EBV, provided by the ACSR, we were able to determine that p24+ ARLs were generally of B cell origin but did not have a specific immunophenotype. In contrast, EBV+ ARLs were more likely to express MUM1 or blimp and less likely to express CD29, CD10 or BCL6. EBV status was not associated with a pre/post HAART diagnosis (44 vs. 40%). However, a subset of EBV-/p24+ tumors was identified. In the pre-HAART era, 13% of the tumors were EBV-/p24+ compared to 30% in the post-HAART era suggesting, that the incidence of this tumor type is increasing (p<0.05). These data describe for the first time the existence of potentially tumor specific HIV in up to 1/3 of all post HAART ARLs, a class of tumor that is immunophenotypically distinct from EBV+ ARLs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5353.

HIV Viremia and the Development of AIDS‐Related Lymphoma in Patients Treated with Highly Active Antiretroviral Therapy

The introduction of highly active antiretroviral therapy (HAART) in the mid1990s for the treatment of human immunodeficiency virus (HIV) infection was associated with a rapid reduction in the incidence of most AIDS-defining events. Although early studies suggested that HAART appeared to have a less dramatic effect on the incidence of AIDS-related lymphomas, particularly non-Hodgkin lymphoma (NHL), than on the incidence of other AIDS-related events [1, 2], subsequent studies confirmed that the incidence of these events had also decreased [3-6]. In the CASCADE (Concerted Action of SeroConversion to AIDS and Death in Europe) Collaboration, the incidence of NHL decreased by 75% from the period before 1997 to 1999-2002 [3]. Among participants in the Swiss HIV Cohort Study [4], the incidence of NHL decreased from 13.6 cases/1000 person-years during the period from 1993 to 1995 to

HIV Viremia Linked with Lymphoma Risk in ART-Treated Patients

Although the incidence of AIDS-related lymphoma has decreased substantially since the development of effective combination antiretroviral therapy (ART), cases still occur even in treated patients, and the lymphomas remain prominent causes of AIDS-related mortality. Repeatedly identified predictors of lymphoma include both nadir and current CD4-cell counts, but considerable data indicate that …

Actual status of AIDS-related lymphoma management in Japan

Recently, with the widespread use of highly active antiretroviral therapy (HAART), the occurrence of opportunistic infections as an acquired immunodeficiency syndrome (AIDS)-defining illness (ADI) has declined dramatically [1]. Decreases in the incidence of AIDSrelated lymphoma (ARL) are not as evident compared with other ADI, so lymphoma has now become one of the most common ADIs [2]. Lymphoma has also become a more common cause of mortality due to AIDS. Management of ARL is starting to represent a critical problem in the total care of the Human Immunodeficiency virus (HIV)-infected

0148 THE NATIONAL EARLY ONSET PSYCHOSIS STUDY: PHENOMENOLOGY AND CLINICAL FEATURES OF THE FIRST TWENTY-FIVE CASES

Despite the decrease in HIV-associated morbidity and mortality with the advent of highly active antiretroviral therapy (HAART), the incidence of AIDS-related lymphoma (ARL) has not decreased as significantly. Therefore, we compared epidemiologic, immunologic, and clinical characteristics of patients diagnosed with ARL in the pre-HAART and HAART eras. We used the Adult and Adolescent Spectrum of HIV-Related Diseases database of Public Health-Seattle and King County to determine incidences and trends among patients with ARL in Seattle/King County, WA. We noted a significant decrease in the incidence of HAART-era patients with ARL (36.6 vs. 8.4 per 1000 personyears). The percentage of women (2% vs. 14%), minorities (black patients 9% vs. 29%; Hispanic patients 6% vs. 21%; Native American patients 0 vs. 14%), and individuals originating from outside the United States (10% vs. 29%) increased significantly. There was also a significant increase in patients diagnosed with ARL at CD4+ counts ≥ 200 cells/μL (3% vs. 21%) and a large decrease in median HIV-1 viral loads at ARL diagnosis (264,667 copies/mL vs. 35,500 copies/mL). Median survival time increased from 3 months to 13 months, and there was a significant decrease in comorbid opportunistic illnesses (83% vs. 36%). In conclusion, ARL incidence decreased significantly and patient profiles changed substantially in the Seattle/King County ASD project. HAART-era patients with ARL were more likely women, minorities, have improved immunologic status, and fewer comorbid opportunistic illnesses. This changing profile of patients with ARL parallels larger changes seen among the general AIDS population in the HAART era.

Changing incidence and prognostic factors of survival in AIDS-related non-Hodgkin's lymphoma in the era of highly active antiretroviral therapy (HAART)

Non-Hodgkin's lymphoma is an AIDS-defining disease. The impact of HAART on the epidemiology and prognosis is debated controversially. A retrospective analysis has been performed in order to determine the influence of HAART. We collected data of 214 cases of AIDS-related Lymphoma (ARL) treated at our centre from January 1984 until May 2003 and analysed them using the Kaplan-Meier-, log rank- and Cox proportional hazard-model. The incidence of ARL increased between 1991 and 1994 up to a peak of 14.83 per 1000 patient years. In the subsequent periods from 1995 onwards however, it decreased to 3.7 in 1000 patient years. The incidence of AIDS-related primary CNS lymphomas (PCNSL) took a comparable, yet more pronounced development. Using the univariate Kaplan-Meier analysis prolonged survival was significantly associated with the achievement of a complete remission as well as with a favourable virological response to HAART. No significant differences could be shown for the use of protease inhibitors as well as for virological response being achieved before the diagnosis of NHL. When using the Cox model, complete remission overrides viral response and thus remained the only independent prognostic factor. Classical prognostic factors (CD4 count, prior Kaposi Sarcoma, extranodal manifestation, staging and histological subtype of NHL) were no longer significant for HAART patients in the multivariate analysis. These results illustrate the requirement for new prospective studies in order to determine the best options and ideal timing of coadministering chemotherapy and the type of HAART. Furthermore this study demonstrates that HAART decreases the incidence of ARL, and that achievement of a complete remission in patients suffering from ARL is--according to the multivariate analysis--the single most important prognostically relevant factor with respect to the time of survival.

Changing Pattern of AIDS: A Bone Marrow Study

We compared bone marrow findings in 2 groups of patients with AIDS during 2 different periods: group 1, n = 20; male/female ratio, 19/1; and group 2, n = 120; male/female ratio, 6/1. Bone marrow iron stores were decreased significantly in group 2 (P < .01), and the incidence of AIDS-related lymphomas was higher, with frequent bone marrow involvement. Two group 1 patients had Kaposi sarcoma, and a 21-month-old girl with transfusion-transmitted AIDS had Burkitt-like lymphoma. In group 2, 44 patients had a history of malignant neoplasms, including Kaposi sarcoma (10 cases), hematologic neoplasms (33 cases), and metastatic leiomyosarcoma (1 case). Of the 120 patients, 15 (12.5%) had bone marrow involvement by malignant neoplasms. The majority of the non-Hodgkin lymphomas were high-grade lymphomas. Patients with AIDS-related malignant neoplasms had higher CD4+ cell counts and viral loads than patients without malignant neoplasms (P < .01, P < .05, respectively). The finding of decreased iron stores in patients with AIDS might aid clinical management of their anemia. The increased incidence of malignant neoplasms, especially lymphomas, in recent years might be related to prolonged survival but with incomplete reconstitution of immune function after antiretroviral therapy.

Changing Pattern of AIDS

We compared bone marrow findings in 2 groups of patients with AIDS during 2 different periods: group 1, n = 20; male/female ratio, 19/1; and group 2, n = 120; male/female ratio, 6/1. Bone marrow iron stores were decreased significantly in group 2 ( P < .01), and the incidence of AIDS-related lymphomas was higher, with frequent bone marrow involvement. Two group 1 patients had Kaposi sarcoma, and a 21-month-old girl with transfusion-transmitted AIDS had Burkitt-like lymphoma. In group 2, 44 patients had a history of malignant neoplasms, including Kaposi sarcoma (10 cases), hematologic neoplasms (33 cases), and metastatic leiomyosarcoma (1 case). Of the 120 patients, 15 (12.5%) had bone marrow involvement by malignant neoplasms. The majority of the non-Hodgkin lymphomas were high-grade lymphomas. Patients with AIDS-related malignant neoplasms had higher CD4+ cell counts and viral loads than patients without malignant neoplasms ( P < .01, P < .05, respectively). The finding of decreased iron stores in patients with AIDS might aid clinical management of their anemia. The increased incidence of malignant neoplasms, especially lymphomas, in recent years might be related to prolonged survival but with incomplete reconstitution of immune function after antiretroviral therapy.

Therapeutic Challenges of AIDS-Related Non-Hodgkin's Lymphoma in the United States and East Africa

Non-Hodgkin's lymphoma (NHL) remains the second most common malignant complication in patients with human immunodeficiency virus (HIV) infection. As we enter the third decade of the acquired immunodeficiency syndrome (AIDS) epidemic, it is apparent that the evolution of antiretroviral therapy and the emergence of combination antiviral strategies have greatly affected the natural history of HIV infection and its neoplastic complications. For example, there may be a trend for declining incidence of AIDS-related lymphoma in the United States for the first time. However, in regions of the world where the burden of HIV infection is greatest, such as in East Africa, AIDS-related lymphoma is an increasing cause of morbidity and mortality. Treatment of lymphoma has evolved coincident with improvements in antiretroviral therapy. Infusional chemotherapy regimens may offer advantages over other regimens and schedules, but comparative trials have not been done. Clinical trial data are available on which to develop therapeutic strategies to treat this disease in East Africa where pragmatic approaches are needed. Both the differences in manifestations of HIV infection and the inherent difficulties in administering cytotoxic chemotherapy in this part of the world must be taken into consideration in planning therapeutic strategies. Improved understanding of the pathogenesis of HIV infection and lymphoma will likely yield improved therapeutic interventions as well.

Management of AIDS-related non-Hodgkin's lymphomas.

The incidence of non-Hodgkin's lymphoma in individuals infected with HIV is approximately 60- to 100-fold increased over the general population. The majority of patients with AIDS-related lymphoma (ARL) present with stage III-IV disease and with B-symptoms. They often have multiple extranodal localisations, with a high incidence of central nervous system involvement. Histologically, most tumours are either diffuse large cell lymphomas or Burkitt lymphomas. Several factors, such as disrupted immune surveillance, Epstein-Barr virus infection, chronic antigenic stimulation, cytokine dysregulation and the acquisition of genetic lesions, are thought to contribute to the pathogenesis. Patients with ARL have a poor prognosis: overall survival ranges from 1.5 to 18 months. The most important adverse prognostic factors are poor performance status, a low CD4+ cell count and a history of opportunistic infections. Results of treatment with polychemotherapy compare unfavourably to results in patients without HIV infection. Since the advent of highly active antiretroviral therapy (HAART), there appears to be a decrease in the incidence of ARL. In addition, the use of HAART in combination with chemotherapy and the use of new treatment modalities may improve the outcome of this disease.

Ovarian Burkitt lymphoma: Pelvic pain in a woman with AIDS

Non-Hodgkin lymphomas, a common AIDS-defining manifestation of human immunodeficiency virus (HIV), are aggressive, advanced at diagnosis, and tend to involve extranodal sites. Burkitt lymphoma comprises approximately 20% of AIDS-related non-Hodgkin lymphomas. Sites frequently affected by the disease include the central nervous system, bone marrow, gastrointestinal tract, and mucocutaneous tissue. Gonadal involvement is less common; reports of testicular lymphomas in adult males with AIDS have been sporadic. Ovarian involvement in AIDS-related lymphoma is exceedingly rare and usually involves pediatric patients. We report an unusual case in which disseminated Burkitt lymphoma presented as pelvic pain in a 32-year-old woman with AIDS. At laparoscopy, the ovaries were unremarkable in appearance but at the upper limits of normal size. However, extreme friability of the left ovary led to hemorrhage and oophorectomy. Pathologic evaluation of the ovary resulted in the diagnosis of Burkitt lymphoma. With improved survival because of antiretroviral therapy, the incidence of AIDS-related lymphomas is expected to rise. Lymphoma should be considered in the differential diagnosis of women with AIDS with perplexing abdominal or pelvic symptoms.

AIDS-Related Lymphoma in Brazil:Histopathology, Immunophenotype, and Association With Epstein-Barr Virus

The occurrence of malignant lymphoma is an increasingly important cause of morbidity and mortality in AIDS patients. The incidence of AIDS-related lymphoma in some developing countries such as Brazil is increasing as the survival of HIV infection has improved. Although there is a clear association between several types of immunodeficiency-related lymphomas and Epstein-Barr virus (EBV), the association of EBV infection in AIDS-related lymphoma in Brazil, where the incidence of AIDS is high, is unknown. Formalin-fixed, paraffin-embedded tissue from 24 cases of AIDS-related lymphoma in Brazil were analyzed for morphologic classification, immunophenotype, and EBV association using in situ hybridization studies with an EBV-EBER1 biotinylated probe. Twenty cases of AIDS-related lymphoma were classified as non-Hodgkin's lymphoma and four cases were Hodgkin's disease. Eleven non-Hodgkin's lymphomas were classified as diffuse large cell type, five cases were small non-cleaved cell, Burkitt-type, and four cases were large cell immunoblastic non-Hodgkin's lymphoma. Eighteen cases were of B-cell phenotype; one was a T-cell lymphoma, and one was classified as null. Epstein-Barr virus (EBV) was demonstrated in the majority of tumor cells of 11 of 20 (55%) of the cases non-Hodgkin's lymphomas and in 3 of 4 (75%) cases of Hodgkin's disease. AIDS-related lymphomas in Brazil are usually of large cell/immunoblastic type, but Hodgkin's disease is also seen. Both non-Hodgkin's lymphoma and Hodgkin's disease are often associated with EBV infection. The non-Hodgkin's lymphoma is predominantly of B-cell phenotype.